Pharmacologic approaches to psychogenic polydipsia: Case reports

Prug. Neuru-Psychophurmacol. h Biol. Psychiat. Printed in Great Britain. All rights reserved.

1986.

PHARMACOLOGIC

Vol. 10, pp. 95-100 Copyright

APPROACHES TO PSYCHOGENIC CASE REPORTS

0

027R-584w36 $0.00 + .50 1986 Pergamon Press Ltd.

POLYDIPSIA:

ROGER G. KATHOL,l JAM4ESA. WILCOX,2 RICI$ D. TURNER,’ ZIAD KRONFOL, STEPHEN C. OLSON 1,495 2 3Department of Psychiatry, College of Medicine ’ Psychiatric Hospital, The University of Iowa Iowa City, Iowa, U.S.A. (Final form,

July 1985)

Abstract -Ziad Kronfol and Stephen C. Kathol, Roger G., James A. Wilcox, Rick D. Turner, polydipsia : Case Reports. Pharmacologic psychogenic approaches to Neuro-Psychopharmacol. 6 Biol. Psychiat . 1986, -10 ( 1) : 95- 100. 1. 2. 3. 4. 5.

Olson: Prog.

Psychiatric patients presenting with chronic psychogenic polydipsia are often difficult to treat with standard psychiatric interventions. Pharmacologic intervention was attempted in three patients and was successful in one. One patient had a significant and sustained reduction of water intake while on 160 mg of propranolol. One patient did not improve with either propranolol or captopril while a third patient showed no improvement of serum sodium with demeclocycline nor reduction of water intake with propranolol. The potential mechanisms by which these pharmacologic agents might alter thirst in patients with primary polydipsia are discussed.

Keywords:

captopril,

Abbreviations tes insipidus

: (DI)

polydipsia,

propranolol,

thirst

angiotensin I converting enzyme (ACE), computed tomography , syndrome of inappropriate antidiuretic hormone (SIADH)

(CT),

diabe-

Introduction Psychogenic polydipsia is loosely defined as excessive fluid intake due to psychological Although believed to be an uncommon syndisturbance (Barlow and DeWardenger, 1959). drome based on its infrequent reporting in the literature, Blum et al. (19831 found excessive fluid intake in 1’7% of hospitalized psychiatric patients using low urine specific gravity as the indicator, while Jose and Perez-Cruet (1979) identified 16 of 239 (6.6%) patients in a large state mental hospital as having histories consistent with compulsive water drinking. Over a 9 month period, three patients were admitted to our hospital who demonstated chronic excessive fluid intake which led to medical compiications on more than one occasion. Because other forms of therapy had proven ineffective in controlling fluid intake, several pharmacotherapeutic measures were instituted to either control drinking behavior or help control the complications of excessive water drinking. This paper reports the results of these interventions. 1. 2. 3. 4. 5.

M.D., D.O., M.D., M.D., M.D.,

Assistant Professor of Psychiatry F.A.C.P., House Staff House Staff Assistant Professor of Psychiatry Fellow Associate

95

and Internal

Medicine

R. G. Kathol et al.

96

Case Reports Case 1 - Renal Complications

and a response

to Propranolol

A 31 -year-old male with chronic disorganized schizophrenia had had auditory hallucinations and thought disorder dating from the age of 17. For the past 7 years he had As a result of his excessive fluid intake the consumed up to ten liters of water per day. patient developed megalocystis (Tank et al., 1980) with renal insufficiency secondary to urinary reflux. At admission the patient’s water intake was 8 liters per day. Concurrent serum and urine osmolalities were 274 and 168 milliosmoles per liter respectively while serum Central and sodium ranged between 120 and 130 meqlliter during hospitalization. nephrogenic diabetes insipidus were ruled out with a water deprivation test (Miller et al., 1970). Other known causes of excess fluid intake such as diabetes mellitus, renal failure, or drug effects (lithium carbonate, demeclocycline, methoxyhypokalemia , hypercalcemia, Computed tomography of the head and flurane, diuretics, or alcohol) were not present. thyroid function tests were normal. Renal insufficiency was reflected by a BUN of 48 mgfdl, serum creatinine of 2.6 mgidl, and creatinine clearance of 54 ml/min. Attempts at behavior modification were uniformly unsuccessful. Because a previous case report indicated that propranolol had been found effective in “compulsive water drinking” to 160 mg (Shevitz et al., 19801, propranolol was started. After the dosage was increased the remainder of per day, water intake decreased to about 1.5 liters per day throughout the hospitalization. Serum sodium gradually rose and was maintained above 140 meq/liter. During the entire hospital stay the patient’s psychosis was treated with 150 mg of molindone HCL. He was transferred to his referring facility with reduced fluid intake but no change in his psychosis. Follow-up 12 months later indicated that the patient continued to ingest only 1.5 liters of fluid per day while on propranolol and had maintained serum sodium levels of 140 meqlliter. Case 2 - A Trial with Captopril The second patient is a 42-year-old male who had a long history of organic mental disorder typified by a full scale IQ of 75, seizure disorder, and continuous auditory and visual hallucinations. He had suffered a skull fracture at the age of 12 months and subsequently developed a large left parietal leptomeningial cyst. Computed tomography (CT) of the head was consistent with a left parietal leptomeningial cyst, and showed no change over a CT scan obtained several years previously. Electroencephalograms demonstrated diffuse slowing and focal delta/theta activity in the left posterior quadrant. He had been treated with Other causes of polydipsia were excluded and anticonvulsants with good seizure control. thyroid function was normal. During the past three years of chronic institutionalization the patient was noted to drink He was chronically hyponatremic with serum sodium levels ranging from 118 to excessively. On at least one occasion he was admitted to our hospital for treatment 128 meq per liter. of seizures secondary to a serum sodium of 110 meq/l. On admission the patient was hallucinating and had dereistic thinking with thiothixene 30 mg per day. When given free access to water, It is possible that hypoosmolslity measured at 18 liters in 24 hours. and/or hyponatremia (125 meq/l) might have contributed to the patient’s because his conversation became more logical during the water deprivation

despite treatment consumption was (250-260 mosm/l) mental problems test.

Thiothixene The findings in this patient indicated a severe case of primary polydipsia. and a trial of propranolol HCl to a maximum dosage of 480 mg per day was discontinued, He was next treated with captopril, a competitive did not decrease intake below 17 l/day. and frequent serum inhibitor of angiotensin I converting enzyme, under close observation No neuroleptics were given. On this sodium determinations at a dose of 150 mg per day. The patient was next medication his water intake actually increased to 30 liters per day. given a trial of haloperidol at doses up to 170 mg per day, again without improvement. Since the patient was already producing a very dilute urine, a therapeutic trial with The patient was returned to his referring demeclocycline HCl was not clinically indicated. Antipsychotic medication was discontinued as it did not facilitv in an unimproved condition. Discharge medications were phenytoin 700 mg per day and primidone impro;e his symptoms. Follow-up 12 months later found the patient to 1750 mg per day for his seizure disorder. be drinking 17 liters of water per day and maintaining a serum sodium of 125 meqlliter.

Psychogenic polydipsia

Case 3 - Primary

Polydipsia

with SIADH Treated

Ineffectively

97

with Demeclocycline

The third patient, a 56-year-old male with chronic disorganized schizophrenia, residual phase, had an eight year history of ingesting more than eight liters of water per day. He drank from toilets and urinals if left unattended but denied that he drank excessively. The patient has had frequent episodes of hyponatremia and one generalized seizure when his serum sodium level reached 100 meqlliter. Computed tomography of the head revealed no abnormalities but the electroencephalogram showed diffuse slowing. Thyroid function tests were normal and other causes of polydipsia were excluded. The patient was admitted with a fluid intake of 8 liters and a serum sodium of 120 meqll This was inwhile on propranolol HCI for hypertension at a dosage of 240 mg per day. creased to 320 mg per day with no change in his polydipsia. He refused captopril therapy. In this patient, the syndrome of inappropriate antidiuretic hormone (SIADH) or a reset osmostat intermittently present (Hariprasad et al., 1980). with was Treatment demeclocycline HCl was begun, as suggested by Nixon et al. (1982) at a dosage of 1200 mg dally. Despite this therapy, there was no significant improvement in his hyponatremia. The patient was given thiothixene, 40 mg dally while on demeclocycline and his mental state improved. Since it was not possible to control the patient’s hyponatremia with demeclocycline HCl nor his water intake with propranolol HCl, it was necessary to avoid extremes of hyponatremia by restricting the patient to a locked bedroom at night. This measure allowed for some decrease in total fluid intake while in the hospital however continued behavior therapy proved impractical despite being in a care facility. Follow-up one year later revealed that the patient still drank approximately 8 liters of water/day while maintaining serum sodium levels near 125 meq/liter.

Serious physical complications can be caused by chronic polydipsia associated with schizophrenia or psychotic organic brain syndrome. Symptomatic hyponatremia intermittently occurs and produces a variety of changes in mental activity and neurological functioning (Hariprasad et al., 1980; Gehi et al., 1981; Wasterlain and Posner, 1968; Arieff and Guisado, 1976). Other complications not directly related to change in electrolyte concentrations reflect the sheer volume of fluid ingested. For instance, enlargement of the bladder (megalocystis) may lead to urinary incontinence, hydronephrosis, renal insufficiency, or renal failure (Blum et al., 1983; Tank et al., 1980; Blum and Friedland, 19831. At least 6 deaths have been reported as a direct result of compulsive polydipsia (Blotcky et al., 1980; DiMaio and DiMaio, 1980; Helwig et al., 1935; Raskind, 1974; Rendell et al., 1978). Most have been the result of acute electrolyte disturbance. Chronic polydipsia in psychiatric patients remains difficult to treat. Psychotherapy unhappily does not alter the behavior. Behavior therapy often proves ineffective for two reasons. First, there are few motivating influences stronger than thirst. It is therefore difficult to find positive or negative reinforcers which conveniently and humanely lead to a change in the drinking behavior. an individual from drinkable Second, the logistics of restricting fluid are overwhelming in most settings. Even if fluid restriction can be accomplished in a structured (closed ward) environment, once the patient is released from the hospital it would be difficult to continue. Two forms of pharmacotherapy have recently been used for psychogenic polydipsia--propranolol HCI and demeclocycline HCl (Shevltz et al., 1980; Nixon et al., 1982). In order to understand the rationale for their use and attempts to control drinking with captopril in our patients it is necessary to review briefly the regulation of thirst and fluid balance. The primary regulators of thirst are blood volume and serum osmolality (Martin et al., 1977). Other stimulants of thirst, dipsogens, have been suggested. Of these angiotensin II has received the most attention (Simpson et al., 1978). This substance is formed as an intermediate product of the renin-anglotensin-aldosterone system. In addition to its activities of vasoconstrlction and aldosterone stimulation, angiotensin II increases drinking

98

R. G. Kathol et al.

behavior in some species by stimulating receptors in the septal area and subfornical organ (Simpson et al., 1978; Blass and Moran, 1975; Blass et al., 1974). Knowledge about the dipsogenic activity of angiotensin II in man is limited. Hypothesizing that angiotensin II may be involved in the drinking behavior of patients with primary polydipsia, propranolol and captopril were used in separate trials in an attempt to reduce drinking by decreasing angiotensin II levels. Propranolol inhibits renin release (and thus indirectly angiotensin II) by blocking beta receptors in the kidney (Winer et al., 1969; Michelakis and McAllister, 1972). Such blockade consistently occurs in doses of 160 mg per day of propranolol (Coltart and Shand, 1970; Pettinger et al., 1973). Captopril, which has not been used as a treatment of primary polydipsia, is an inhibitor of angiotensin I converting enzyme (ACE) thus blocking the formation of angiotensin II. All three of the patients in this clinical series received a trial of propranolol. Patient 1 who had developed significant urinary tract symptoms was the only one to respond to this pharmacotherapeutic intervention. Follow up on this patient 12 months later while being maintained on propranolol indicated continued efficacy. Such long term response has not been reported before. The other two patients did not respond. A trial with captopril was attempted in patient 2 despite failure with propranolol because he had run such a difficult and precarious clinical course. Further, during his water deprivation test he had shown significant clinical improvement when his serum osmolality had risen into the normal range, albeit for a short time. Under close observation with frequent checks of serum electrolytes, a trial with captopril revealed an actual increase in fluid intake. There is currently a debate whether captopril administered peripherally will stimulate or inhibit drinking behavior in man. The data concerning its activity on thirst in the rat model are conflicting. Henderson et al. (1979) found that administration of captopril resulted in a decrease in the drinking rate in rats bred for central diabetes insipidus (DI). These results however conflict with Gardiner and Bennett (1983) and Schiffrin and Genest (1982) who found that captopril stimulates drinking behavior in normal rats and rats with DI when given in a higher dose. In man recent evidence suggests that captopril promotes both diuresis and naturesis without apparent increase in thirst in patients with dilutional hyponatremia associated with seSuch treatment resulted in a vere chronic congestive heart failure (Packer et al., 1984). net increase in serum sodium. For this reason a carefully conducted clinical trial in a patient who had already demonstrated significant morbidity from psychogenic polydipsia was Unfortunately no reduction in drinking thought to be indicated under close observation. behavior occurred and since an increase in fluid intake was actually recorded future trials should be performed only in situations in which fluid ingestion can be closely monitored. This medication does not decrease the Patient 3 was given a trial of demeclocycline. Its principal action is that of inhibiting the effect of ADH on the distal intake of fluid. Thus increased tubule and collecting system, producing a nephrogenic diabetes insipidus. Since patient 3 exhibited interfree water clearance leads to an elevation of serum sodium. high for a yet dilute serum, mittent periods when urine osmolality was inappropriately Serum sodium did not significantly increase over the six-week demeclocycline was tried. Demeclocycline has been used course of treatment despite dosages of 1200 mg per day. effectively in one patient with self-induced water intoxication (Nixon et al., 1982) to control The one patient of ours in which this was thought to be a logical option hyponatremia. demonstrated no improvement with its use. Conclusions can cause a Our results support the findings of Shevitz et al. (1980) that propranolol decrease in drinking behavior in patients with primary polydipsia, albeit not uniformly. Demeclocycline has been reported to control hyponatremia in a patient with primary polydipIt is possible that inhibition of the renin-angiotensin sia but was ineffective in our patient.

Psychogenic polydipsia

99

treatment of this condition in a certain subgroup of individuto establish the etiologies of primary polydipsia and controlled pharmacotherapeutic trials are necessary to improve the treatment of this disorder and prevent its complications. system may be useful for als . Continued research

the

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